tbuckley/cabot-search huggingface dataset:
Abstract 14083: Prognostic Utility of Neutrophil Gelatinase-Associated Lipocalin in Predicting Cardiovascular Events in Patients With Stable Coronary Artery Disease Treated With Percutaneous Coronary Intervention
Authors: Chien-Yi Hsu, HSIN-BANG LEU, Jaw W Chen
Journal: Circulation (2022)

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) modulates matrix metalloproteinase-9 thereby affecting the stability of the atherosclerotic plaque. Accumulating evidence showed that high NGAL levels were independently associated with major adverse cardiac events (MACE) and mortality in patients with acute myocardial infarction (MI). However, only few studies have measured NGAL in stable coronary artery disease (SCAD) patients, and no significant prognostic predicting value between NGAL and SCAD has been established yet. Hypothesis: The aim of this study was to investigate the prognostic role of NGAL in a prospective cohort study of patients with SCAD treated with percutaneous coronary intervention (PCI). Methods: In total, 2296 SCAD patients with previous PCI were enrolled in a multi-center prospective observational study. The primary outcome was the occurrence of MACE (cardiovascular death, nonfatal MI and ischemic stroke). The secondary outcome was the occurrence of combined cardiovascular events (including all-cause death, nonfatal MI, nonfatal stroke, revascularization and hospitalization for heart failure). Results: During the mean follow-up period of 4.6 ±1.7 years, 384 patients reached the primary endpoints and 746 patients reached the secondary endpoints. Kaplan-Meier analysis showed that the event-free survival was significantly different in the first tertile and third tertile groups (log-rank test, p&lt;0.001) in subjects categorized by NGAL levels. In multivariate Cox proportional hazard regression analysis, plasma NGAL was independently associated with MACE (adjusted hazard ratio [aHR] 1.24; 95% confidence interval [CI] 1.03-1.50, p=0.02) and the risk of developing combined cardiovascular events (aHR 1.31; 95% CI 1.14-1.51, p&lt;0.001) during follow-up. Conclusions: High plasma NGAL independently associated with the occurrence of MACE and combined cardiovascular events in SCAD patients treated with PCI.
Abstract 14277: Comparison of Three Vascular Closure Devices for Vascular Access Closure After Cardiac Electrophysiology Procedures
Authors: Carola Gianni, Thomas Chafizadeh, Domenico G Della Rocca, Sanghamitra Mohanty, Amin Al-Ahmad, J D Burkhardt, G J Gallinghouse, Rodney P Horton, Patrick M Hranitzky, Javier E Sanchez, Andrea Natale
Journal: Circulation (2022)

Introduction: Vascular closure devices are commonly used for EP procedures to achieve rapid hemostasis. Different devices using different mechanisms of action are available, but the potential contribution of each type to the incidence of vascular complications is not clear. Methods: This is a single center, prospective study in which 138 contemporaneous patients undergoing EP procedures were categorized according to the vascular closure device type used: Vascade (collagen plug, n=57), Perclose (suture, n=41), and SiteSeal (external compression, n=40). The primary endpoint was access-related major vascular complications. Secondary endpoints included time to ambulation and delayed access-site bleeding requiring additional manual pressure. Results Mean age and BMI 68±11 years and 29.7±6.2 Kg/m 2 , 46 (33%) were female, 121 (88%) were on uninterrupted antithrombotic therapy (71% OAC, 14% OAC/APLT, 3% APLT). Femoral vein access was obtained in all, bilaterally in 113 (82%), with a mean of 3±1 access sites per patient and a sheath size ranging from 6- to 23-Fr. Femoral arterial access was obtained in 14 (10%), once per patient, with a sheath size ranging from 5- to 8-Fr. There were no arterial access complications. On the venous side, hematomas occurred in 3/57 (5%) of the Vascade group, 1/41 (2%) of the Perclose group, and 0/40 (0%) of the SiteSeal group (p=ns for all comparisons). Delayed access-site bleeding occurred in 5/57 (9%) of the Vascade group, 5/41 (12%) of the Perclose group, and 7/40 (18%) of the SiteSeal group (p=ns for all comparisons). Time to ambulation was comparable between groups (minutes: 139±51 Vascade, 137±34 Perclose, 123±11 SiteSeal, p=ns). Conclusion Vascade, Perclose, and SiteSeal are comparable in term of vascular complications and time to ambulation for patients undergoing EP procedures.
Abstract 13427: Bleeding in Morbidly Obese Patients Treated With Direct Oral Anticoagulants Compared to Warfarin: The Michigan Anticoagulation Quality Improvement Initiative Experience
Authors: Nelish Ardeshna, Thane Feldeisen, Xiaowen Kong, Brian Haymart, Mona Ali, Vinay Shah, Geoffrey Barnes, James B Froehlich
Journal: Circulation (2022)

Introduction: Direct Oral Anticoagulants (DOACs) have overtaken warfarin in the treatment of non-valvular Atrial Fibrillation (AF) and venous thromboembolism (VTE). However, there is very limited data that explores the safety of DOACs for patients that are morbidly obese (BMI &gt;40). Methods: In this multi-center retrospective study, we sought to use the Michigan Anticoagulation Quality Improvement registry (MAQI) to see how treatment of non-valvular AF or VTE with DOAC vs. warfarin affects bleeding in morbidly obese patients. Specifically, we compared average major, clinically relevant non-major (CRNM), and minor bleeding events per 100 patient years that were adjusted for statistically significant baseline characteristics (p&lt;0.05). Results: There were a total of 1028 patients with BMI &gt;40 included in the registry between June 2015 and September 2019. 434 patients were treated with DOACs, while 594 patients were treated with warfarin. Baseline characteristics between the two groups included age (61.5 vs 57.8, p&lt;0.001), gender (63.6% vs 61.1% female, p=0.42), race (76.5% vs 64.3% white, p&lt;0.001), and HAS-BLED score (2.3 vs 2.3, p=0.96). The DOAC treated group had a higher event rate of major (4.3 vs 3.7, p=0.006), CRNM (10.7 vs. 7.4, p=0.002), and minor bleeding (19.1 vs. 13.2 p&lt;0.001) compared to the warfarin treated group. Conclusions: There is a higher rate of major, CRNM, and minor bleeding in morbidly obese patients treated with DOAC compared to warfarin. Further studies to compare the two anticoagulants and understand bleeding drivers in this population are needed.
Abstract 13816: The Hypertension Care Cascade in 2019-21: A Nationally Representative Study of 1.9 Million Adults in India
Authors: Jithin Sam Varghese, Mohammed K Ali
Journal: Circulation (2022)

Introduction: Previous studies from India reported management of hypertension (diagnosed: 45%, treated: 13%) among adults 15-49 years, a fraction of those suffering from disease. This study aimed to provide nationally-representative estimates of (i) the proportion of all adults (18+ years) with prehypertension and hypertension (HTN), and (ii) the heterogeneity in their cascade of care by natal sex, age, and urbanicity. Methods: Using data from non-pregnant women (n = 959,468) and men (n = 935,829) in the National Family Health Survey-V (2019-21), we estimated the sex-specific prevalence of prehypertension and HTN (see footnotes of Figure ), and among adults with HTN, the self-reported care cascade (ever screened, diagnosed, taking medication, under control defined by normotension). All estimates incorporated the complex survey design and were stratified by urban versus rural or by age group (18-39, 40-64, 65+). Results: Nationally, the prevalence of prehypertension and HTN were 19.1% (95%CI: 18.9,19.2) and 27.7% (95%CI: 27.5, 27.8) respectively. The prevalence of prehypertension was similar in urban areas (vs rural) among men (%; 23.2 vs 21.7) and women (%; 16.7 vs 16.1). Prevalence of HTN was higher in urban areas (vs rural) among men (%; 30.9 vs 27.2) and women (28.8 vs 26.2). Both prehypertension and HTN were higher with increasing age. Prevalence of screening in the total population was 56%, and was higher in urban areas, among women and higher with age. Among those with HTN, only 40%, 23%, and 10% being diagnosed, taking medication, and under control, respectively. Diagnosis, treatment and control were higher in urban areas, women, and older age groups ( Figure ). Conclusions: Despite the high prevalence of hypertension, there is a high unmet need at each step of care cascade nationally, especially in rural adults. Moreover, the prevalence of prehypertension is high in rural areas, and those under 40 years, requiring a comprehensive approach for prevention and management.
Abstract 12998: Incidence, Complications, and Outcomes of High Degree Atrioventricular Block in Patients With Sarcoidosis
Authors: urza Niroula, Tanveer Mir, Tanveer Hussain, Waqas Qureshi, Layla Shanah, Muhammad S Khan, Mohammed Uddin, Hamza Tahir, Bhanu Maturi, Tilachan Parajuli
Journal: Circulation (2022)

Introduction: High degree atrioventricular block (AV block) is known to occur in patients with sarcoidosis. The incidence, complications and outcomes of high degree AVB in sarcoidosis patient is unknown. We aimed to analyze a national database to evaluate the epidemiological characteristics of AVB in sarcoidosis patients. Method: We included 110,264 sarcoidosis adult patients (age ≥18 years) hospitalized in 2019 from the Nationwide Readmission Database (NRD). Baseline demographics, comorbidities, and outcomes were identified using International Classification of Diseases (ICD) codes. High degree AVB was defined as Mobitz type II and complete heart block. Results: Of the total, 2336 (2.1%) sarcoidosis patients (mean age 61.0 ± 14.0 years and 52.8% females) were admitted with AVB. Of these, 71 (3.02%) patients died in the AVB group and 2691(2.49%) in the non AVB group (p &gt;0.05). Complications were noted to be higher in AVB group vs. non AVB group (34.9% vs. 28.5%) but was not significantly associated with AVB (OR 1.03, CI (0.87- 1.23), p=0.7). The commonest complications were acute kidney injury (26.1% vs. 21.4%), cardiac arrest (2.64% vs 0.84%) and device related infection (1.89% vs 0.33%) that were significantly more than non AVB group with p&lt;0.05. The cost of index hospitalization was higher for patients with AVB, but the length of stay was similar. The readmission rates or mortality is not associated with diagnosis of AVB on presentation. Conclusion: In hospitalized sarcoidosis patients, high degree AVB was not associated with increased risk of mortality or readmissions but with higher cost of hospitalization. In these patients, cardiac risk factors were associated with complications.
Abstract 12792: Reentrant Drivers Are Distinguished From Passive Rotors by Sequential Computer Simulation of Ablation Using Personalized Non-Paroxysmal Atrial Fibrillation Heart Models Based on Late Gadolinium Enhancement Magnetic Resonance Imaging (LGE-MRI)
Authors: Kensuke Sakata, Ryan Bradley, Syed Yusuf Ali, Carolyna Yamamoto Alves Pinto, Shane Loeffler, Eugene G Kholmovski, Adityo Prakosa, Natalia Trayanova
Journal: Circulation (2022)

Introduction: Although rotor modulation targeting atrial fibrillation (AF) drivers or substrates has been proposed as one of the effective ablation strategies for non-paroxysmal AF (Non-PAF), previous meta-analyses demonstrated that ablation added to pulmonary vein isolation (PVI) did not result in the expected outcome. This is because the optimal method of detection of rotors and ablation strategy remain unclear. Recently, rotor detection using LGE-MRI-based computer simulations has been shown to be effective for Non-PAF ablation in clinical practice. Our study aimed to establish the minimal ablation strategy that, while correctly finding the rotors, also avoids iatrogenic atrial tachyarrhythmias due to excessive ablation. Hypothesis: By prioritizing and classifying detected rotors, reentrant drivers (RDs) of AF rather than passive rotors (PRs) could be identified, thereby offering an optimal ablation strategy. Methods: Personalized computational modeling of AF ablation was performed in 10 Non-PAF patient models based on fibrosis data from LGE-MRI. In each bi-atrial model, all rotors induced outside of PVI were investigated, and a number of ablation strategies were examined sequentially to classify rotors and achieve minimal ablation (figure). A rotor that terminated following ablation of another rotor was defined as PR. A rotor that persisted and needed to be ablated to achieve non-inducibility of the substrate was defined as RD. Results: Seven patients had rotors outside of PVI, with 6 having both PRs and RDs. Overall, 35 rotors were induced, 13 in left atrium and 22 in the right; 17 were RDs and 18 PRs. In addition, the density of fibrosis in the sites of RDs was significantly higher than in those of PRs (p=0.031). Conclusion: The sequential computer simulation strategy to predict ablation targets using a personalized AF model is promising in detecting different types of rotors and establishing the optimal minimum-lesion ablation strategy.
Abstract 14131: Early Experience With a Novel Extravascular Pacemaker Lead
Authors: Sarin N Paluri, Wesley Chin, Vijay Kurup, Abhishek Pandravada, ann impens, Martin C Burke
Journal: Circulation (2022)

Introduction: Transvenous pacemaker leads (TVL) provide electrical support for symptomatic bradycardia patients but requires wiring the vasculature and heart. TVLs create complications such as bleeding, infection and cardiac perforation. We examine here a novel method to deliver an extravascular pacemaker lead (EVL) via the anterior chest without touching the heart. Hypothesis: This novel AtaCor extra cardiac pacemaker lead will achieve appropriate pacing in an ambulatory model without significant macro- or micro-dislodgement. Methods: 4 patients were enrolled to evaluate prototype EVLs for performance and safety. The patients were indicated for permanent pacemaker insertion as an index procedure. The study involved a similar paddle lead that was specifically designed for the anterior mediastinal space. The leads were matched to a delivery tool and delivered via the anterior parasternal left chest. We are developing a sustainable pacing system that provides capture without touching the heart in an ambulatory patient. The imaging was performed by fluoroscopy and x-ray. The position, stability of the lead and the electrical performance will be described in detail and related to the imaging results for up to 7 days in an ambulatory patient as a self-control. Results: Stable group (2 patients) showed no micro-dislodgement on fluoroscopic imaging with simultaneous successful pacing. Unstable group (2 patients) showed micro-dislodgement on fluoroscopic imaging which was correlated to poor pacing capture. No patients showed macro-dislodgement on chest x-ray (PA and Lateral). Conclusions: AtaCor’s novel extra cardiac pacemaker lead successfully gains temporary pacing. However, due to the size of the cathode electrode, there are limitations in the ambulatory patient population. We recommend the development of further prototype iterations based on this data.
Abstract 12752: Ultrasound-Responsive Liposome Enhanced Gene Delivery for Heart Disease
Authors: Xing Yin, Brion Frierson, Jean G Wu, Melanie R Moody, Heinrich Taegtmeyer, James F Martin, David D McPherson, Shaoling Huang
Journal: Circulation (2022)

Introduction: Genome editor-CRISPR/Cas9 holds much promise for treatment of heart disease. A critical step is the development of gene transfer platform that can deliver genes into heart muscle efficiently. We have developed ultrasound (US)-responsive echogenic liposomes (ELIP) for controlled payload release, and enhanced payload penetration upon ultrasound application. Hypothesis: We hypothesize that ELIP in combination with ultrasound application can enhance gene delivery in cardiomyocytes. Methods: FITC (green fluorescence) labeled NF-kB oligonucleotides were used as a prototype for gene delivery. ELIP containing NF-kB-FITC (ELIP-NF-kB-FITC) were prepared by a conventional procedure of hydrating the lipid film, sonication, freezing and drying. Rats were divided into control, ELIP-NF-kB-FITC without US, and ELIP-NF-kB-FITC with US. ELIP-NF-kB-FITC were administered into the left ventricle by injection with the aorta clamped. Ultrasound (1 MHz at 0.5 W/cm2, 100% duty cycle) was applied to the heart for 5 min. Thereafter, heart was excise, fixed and imaged by fluorescent microscopy. The fluorescent intensity of the left ventricular wall was quantified by NIH ImageJ software. Results: ELIP-NF-kB-FITC delivered without ultrasound application showed limited green fluorescence in the heart. Ultrasound (US) in combination with ELIP enhanced NF-kB-FITC penetration into the ventricular walls (Fig. 1A). Quantitatively, ultrasound provided 2-fold increase (2.0 ± 0.27, P &lt; 0.01 vs control) in the mean green fluorescence (Fig. 1 B). Conclusions: Ultrasound application in combination with ELIP enhanced gene delivery into the ventricular walls. This platform offers a promising delivery system of CRISPR components for the correction of cardiomyopathies caused by gene mutation/change.
Abstract 12879: Endothelial Cu Exporter Atp7a Deficiency Promotes Cu-Dependent Endothelial-to-Mesenchymal Transition and Atherosclerosis via Orchestrating Glycolysis and Ros Signaling
Authors: Dipankar Ash, Seock-Won Youn, Sudhahar Varadarajan, Archita Das, Yali Hou, Malgorzata McMenamin, Harriet Boatwright, Bradford G Hill, Jack H Kaplan, Masuko Ushio-Fukai, Tohru Fukai
Journal: Circulation (2022)

Introduction: Oxidative stress, inflammation and metabolic reprogramming contribute to endothelial cell (EC) dysfunction and atherosclerosis. Copper (Cu), an essential micro-nutrient, promotes atherosclerosis via unknown mechanism. Since excess Cu is toxic, bioavailability of intracellular Cu is tightly controlled by Cu exporter ATP7A. However, the role of ATP7A and its molecular linkage with inflammation, oxidative stress and metabolism in EC dysfunction and atherosclerosis are entirely unknown. Results: Here we found a dramatic reduction of ATP7A expression in human and mouse atherosclerotic aorta. Surprisingly, ATP7A knockdown (KD) in human aortic ECs using shRNA changed the cell morphology from EC to mesenchymal types. This was confirmed by RNAseq/qPCR showing reduced EC markers and increased mesenchymal markers, indicating endothelial to mesenchymal transition (EndMT). Mechanistically, loss of ATP7A in ECs increased [Cu]i and PFKFB3-dependent glycolysis (1.8- fold by ECAR in Seahorse assay). Overexpression of PFKFB3 or constitutively active PFK2, which enhances glycolysis, or direct Cu treatment induced EndMT. In parallel, ATP7A KD in ECs increased mitochondrial (mito)ROS (9.8 fold)-histone demethylase JMJD2B, which induced inflammatory EndMT inducer TGFβ2-EndMT transcription factor Snail (2 fold) axis. Of note, ATP7A KD-induced glycolysis as well as mitoROS- TGFβ2-Snail axis involved in EndMT were inhibited by Cu chelator TTM. In vivo, Cu transport dysfunctional ATP7A mutant/ApoE -/- mice showed enhanced atherosclerosis and CD31 + /αSMA + cells representing EndMT in aorta compared to control ApoE -/- mice, which was further confirmed by EC-specific ATP7A -/- /mTmG reporter mice. Conclusion: Our study demonstrates that ATP7A dysfunction in ECs drives EndMT by orchestrating mitoROS-JMJD2B-TGFβ as well as PFKFB3-glycolysis axis in a Cu dependent manner, leading to Snail induction to accelerates atherosclerosis. Thus, ATP7A is a potential therapeutic target for treatment of inflammatory vascular disease.
Abstract 13388: Age-Stratified Sex Differences in COVID-19 Hospital Outcomes
Authors: Jian Chu, Margaret Brandon, Sven Wang, Manali Shah, Jeanne Du-Fay-de-Lavallaz, Annabelle S Volgman, tisha suboc, Kim A Williams
Journal: Circulation (2022)

Introduction: Sex differences in COVID-19 outcomes are well-known and have been ascribed to numerous factors including age-dependent sex hormones. We hypothesize that the protective effect of female sex in hospitalized COVID-19 patients attenuates with age. Methods: We retrospectively analyzed patients who were hospitalized for COVID-19 infection at three hospitals of the Rush University System for Health (RUSH) (Chicago, IL) between March to December 2020. The primary endpoints were in-hospital mortality and major adverse cardiovascular events (MACE), defined as a composite of acute myocardial infarction, cardiac arrest, acute heart failure, and stroke. Stratified logistic regression was performed to estimate the odds ratios of these endpoints in male compared to female patients by age group (&lt;45, 45-55, 55-65, 65-75, and ≥75 years). Results: Of 1705 patients (age 58.1±16.9 years, 54.3% male, 24.6% White) who were hospitalized for COVID-19 infection, 179 (10.5%) patients experienced in-hospital mortality and 290 (17.0%) patients experienced MACE, respectively. The incidence of these outcomes progressively increased with age in both sexes. In patients &lt;45 years of age, there was a trend towards increased risk for in-hospital mortality (aOR 4.47; 95% CI: 0.54 - 42.38) and MACE (aOR 2.43; 95% CI: 0.97 - 6.10) in men compared to women. However, this trend attenuated with increasing age strata and there was a slight decrease in risk for in-hospital mortality (aOR 0.79; 95% CI: 0.39 - 1.58) and MACE (aOR 0.70; 95% CI: 0.38 - 1.28) among middle-aged (55-65 years of age) men compared to women. Conclusions: In this multi-hospital registry of COVID-19 patients, there was a reverse J-shaped trend in odds of in-hospital mortality and MACE in men compared to women. Female sex appeared to be an independent protective factor for adverse hospital outcomes among patients &lt;55 years of age but not among older patients, suggesting a protective role of premenopausal sex hormones.